There are at least five genetically distinct collagen types whose degradation may be controlled independently. The initial step of collagen degradation is performed by collagenase. We were the first to find that type IV basement membrane collagen and type V collagen is not degraded by human skin collagenase suggesting that a separate collagenase may degrade types IV and V collagen. A collagenase which preferentially degrades type IV collagen has been derived from metastatic tumor cells and from mammary epithelium. This collagenase has been purified 1000-fold and its cleavage products have been partially characterized by rotary shadowing electron microscopy. We are further studying the secretion rate of this enzyme by a wide variety of cell types both normal and malignant. A collagenase which preferentially degrades type V collagen has been identified and purified from metastatic tumor cells. Membrane-associated forms of these enzymes have been discovered in migrating endothelial cells responding to a chemoattractant. Polyclonal monospecific antibodies to the type IV collagenase have been prepared. These antibodies react with human breast carcinoma cells in tissue sections. The collagenolytic susceptibility of 1Alpha 2Alpha 3Alpha (a new type of cartilage collagen) has been elucidated.